A single theory for the evolution of sex chromosomes and the two rules of speciation

Sex chromosomes are involved in three major empirical patterns: Y (or W) chromosomes are often non-recombining and degenerate; heterogametic offspring (XY or ZW) from interspecific crosses are more often sterile or inviable than homogametic offspring (Haldane's rule); the X (or Z) has a disproportionately large effect on reproductive isolation between species compared to autosomes (the large X effect). Each observation has received its own tailored explanation involving multiple genetic and evolutionary causes. Here, we show that these empirical patterns all emerge from a single theory for sex chromosome evolution incorporating the co-evolution of cis and trans-acting regulators of gene expression, and leading to systematic misexpression of dosage-compensated genes in heterogametic F1 hybrids, for both young and old sex chromosomes.